Abstract:
:The mechanisms involved in the virulence of Yersinia pestis, the plague pathogen, are not fully understood. In previous research, we found that a Y. pestis mutant lacking the HicB3 (YPO3369) putative orphan antitoxin was attenuated for virulence in a murine model of bubonic plague. Toxin-antitoxin systems (TASs) are widespread in prokaryotes. Most bacterial species possess many TASs of several types. In type II TASs, the toxin protein is bound and neutralized by its cognate antitoxin protein in the cytoplasm. Here we identify the hicA3 gene encoding the toxin neutralized by HicB3 and show that HicA3-HicB3 constitutes a new functional type II TAS in Y. pestis. Using biochemical and mutagenesis-based approaches, we demonstrate that the HicA3 toxin is an RNase with a catalytic histidine residue. HicB3 has two functions: it sequesters and neutralizes HicA3 by blocking its active site, and it represses transcription of the hicA3B3 operon. Gel shift assays and reporter fusion experiments indicate that the HicB3 antitoxin binds to two operators in the hicA3B3 promoter region. We solved the X-ray structures of HicB3 and the HicA3-HicB3 complex; thus, we present the first crystal structure of a TA complex from the HicAB family. HicB3 forms a tetramer that can bind two HicA3 toxin molecules. HicA3 is monomeric and folds as a double-stranded-RNA-binding domain. The HicB3 N-terminal domain occludes the HicA3 active site, whereas its C-terminal domain folds as a ribbon-helix-helix DNA-binding motif.
journal_name
J Bacterioljournal_title
Journal of bacteriologyauthors
Bibi-Triki S,Li de la Sierra-Gallay I,Lazar N,Leroy A,Van Tilbeurgh H,Sebbane F,Pradel Edoi
10.1128/JB.01932-14subject
Has Abstractpub_date
2014-11-01 00:00:00pages
3712-23issue
21eissn
0021-9193issn
1098-5530pii
JB.01932-14journal_volume
196pub_type
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journal_title:Journal of bacteriology
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journal_title:Journal of bacteriology
pub_type: 杂志文章
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更新日期:1991-01-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of bacteriology
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doi:10.1128/JB.83.1.20-26.1962
更新日期:1962-01-01 00:00:00
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更新日期:1986-07-01 00:00:00
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更新日期:1970-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2003-07-01 00:00:00
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journal_title:Journal of bacteriology
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更新日期:1988-11-01 00:00:00
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journal_title:Journal of bacteriology
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更新日期:1999-12-01 00:00:00
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更新日期:1998-01-01 00:00:00
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journal_title:Journal of bacteriology
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journal_title:Journal of bacteriology
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更新日期:2000-04-01 00:00:00
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更新日期:2003-11-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.85.6.1295-1299.1963
更新日期:1963-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:1973-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1979-01-01 00:00:00